Numerous observational studies have shown that an elevated level of total plasma (tHCY) is an independent risk factor for arterial occlusive disease, and is associated with venous thrombosis and pulmonary embolism. Moreover, we have reported that experimental elevation of tHCY in nonhuman primates shows acetycholine-induced arterial relaxation, indicating that elevated tHCY alters vascular function. In the majority of cases, elevated tHCY levels are lowered by treatment with supplemental folic acid. On January 1, 1998, due to such folic acid as known to reduce the risk for neural tube defects (NTD) in the developing fetus, the FDA recommended the fortification of certain foods with folic acid by ~100 ?g/day. Further, to test this hypothesis that nationwide fortification of food with folic acid might reduce tHCY, Malinow et al. conducted a clinical trial using breakfast cereal fortified with different levels of folic acid. Results indicated that such cereals containing folic acid (499 ?g and 655 ?g per 30 g of cereal) lowered similarly tHCY in subjects with coronary heart disease, suggesting that ~400 ?g of folic acid provides maximum effect to lower tHCY. The above study will determine whether folic acid fortification (40 ?g/day) has similar effects as supplementation (2.5 mg/day). In a metanalysis, it has been shown that folic acid supplementation between 0.5 and 5.0 mg/day have similar effects on tHCY levels. FUNDING Homocyst(e)ine testing funds PUBLICATIONS None